Porphyrias and mental handicap.

substances, the main one of which he called haematoporphyrin (porphurouspurple). Three years later Schultz published the first case of porphyria. In 1911 Glinther classified the diseases of porphyrin metabolism from published cases, including his own. Since then, numerous papers have been published and various classifications put forward. The latest classification is that from Brodie et al,2 in which the major sites of abnormal porphyrin production are liver and bone marrow:


4.
Cutaneous hepatic porphyria (a) Genetically predisposed The clinical picture of porphyrias has many facets. It was Waldenstrom5 who in 1939 called porphyrias, like syphilis and hysteria, 'la petite simulatice', and Sikes6 said in 1960: This disease with more faces than Eve should be kept in mind by all practitioners of the healing art, since the histories of many cases show a multitude of inaccurate diagnoses even covering periods of many years'.
Porphyrias show in the acute stage all or various combinations of signs and symptoms of colicky abdominal pain, nausea and vomiting, constipation, loss of weight, ileus, jaundice, fever, leucocytosis, peripheral neuritis, muscular atrophy, neurotic behaviour, delusions, psychosis, convulsions and skin photosensitivity. ECG abnormalities, hypertension, onycholysis, blindness, hypercholesteremia with renal impairment and hyponatremia have also been reported. The photosensitivity effect is responsible for the reddish-pink fluorescence produced by ultraviolet light in the teeth and bones of the cases of congenital porphyria, and of other tissues in cases of hepatic porphyrias.
It has been suggested that these unfortunate individuals suffering from porphyrias have given the legend of the werwolf. Their hairy faces, claw-like hands, red teeth and intermittent mental derangement have, in the primitive mind, imbued them with evil supernatural powers. The red teeth suggest a diet of blood, and photosensitivity of the skin leads to nocturnal rather than daytime sorties.7 Urine in the acute stage has usually a red-wine-like colour (port, burgundy or marsala) which on standing in light becomes dark mahogany-like brown. hereditary coproporphyria with epilepsy in a male (IQ34) was observed by Houston et al14 who reported that they knew of another mentally handicapped patient who developed epilepsy at 3 years of age in whom the diagnosis of porphyria was made at the age of 29. Gregor et al15 described a 6 month old girl with psycho-motor retardation, convulsions and bilateral congenital cataracts who suffered from acute intermittent porphyria.
I am here reporting three further cases of porphyria associated with mental handicap: CASE 1 Male, 38 years of age, IQ68, suffers from superimposed manic depressive psychosis, which has been fairly well controlled with lithium during the past twelve years.
The maternal great grandfather and paternal great grandfather were brothers. There is no other history of mental or physical illness in the family. Pregnancy was full term and normal. He is the youngest of four children. He has had otitis media from two to two and a half years of age. He attended an ordinary school where he frequently displayed bizarre and unusual behaviour. He is said to have walked and talked in his sleep. School examination revealed him to be educationally subnormal. After leaving school he was employed as a general labourer. The patient was admitted when 14 years old to an isolation hospital with symptoms suggestive of polio-myelitis, but this was not confirmed. Since 1953 she has spent her life in various hospitals for the mentally handicapped and has been at Stoke Park Hospital since 1964. In July 1965 she had severe abdominal pains with vomiting followed by jaundice. In August 1968 she was given 400 mgs of quinalbarbitone prior to dental treatment. Next day she started to vomit, collapsed and became comatose. Gradually she responded to treatment but remained ataxic for another two days. Urine examination revealed a positive prophyrine screening test.
Her EEG shows a liability to epileptic states. She suffers from bouts of severe behaviour disorders which are treated with diazepam. CASE 3 Female, 31 years old, IQ 39. A known epileptic since 8 years of age. There is no other history of mental or physical illness in the family. She has one older brother. Her mental handicap was observed at 6 years of age.
She was admitted to Stoke Park Hospital in June 1971 for two weeks' temporary care during her parents' annual holiday. Apart from her epilepsy and mental handicap it was noted that she had a mottled pigmentation of the face and she was passing a reddish dark urine. Repeated examination of urine frequently showed strong positive porphobilinogen and uroporphyrin. The faeces screening test was also positive. Electrolyte levels were within normal limits but her EEG was abnormal. Her anti-convulsive therapy on discharge was primidone and diazepam. I recently inquired, at random, from a few hospitals for the mentally handicapped in the British Isles and I learned of five more cases of porphyria all Vigilance over new drugs and new chemical compounds which may cause porphyria is very important. An example of this is the Turkish epidemic of porphyria which took place in 1954 after seed wheat had ben treated with the fungicide hexachlorobenzene. Over 5000 people were affected, of whom about 4500 were children under 16 years, with a 10% mortality rate (2?5 years 95%).
Inheritance of congenital porphyria in bovines and pigs has also been reported and experimental porphyria were produced with various drugs in dogs, rabbits, rats and fowls.1 Two world congresses on porphyria, one in 1963 (Cape Town) and another in 1975 (Freiburg), contributed greatly towards the diagnosis of porphyria and produced further biochemical evidence regarding its aetiology and pathology. TREATMENT Modern intensive care has done much to lessen the mortality from attacks of acute porphyria from 9% to 30% for a series of patients collected over the past two decades but progress towards an effective, specific treatment has been slow.
Carbohydrate loading is now widely used in the management of acute attacks of porphyria.
Prompt and often dramatic recoveries following haematin infusions have been reported. As with carbohydrate infusions, objective assessment of the effectiveness of haematin infusion is difficult and, promising as it seems, this form of treatment is still under evaluation.
Prevention of the acute attacks remains as important as ever. This approach which is based on diagnosis during the symptomless phase and avoidance of known precipitants has been strengthened by the introduction of erythrocyte uroporphyrinogen?1?synthase measurements for the diagnosis of acute intermittent porphyria and coproporphyrinogen oxidase measurements for hereditary coproporphyria.21 CONCLUSION During the past twenty years great advances have been made regarding diagnosis, classifications and prevention of porphyrias. No doubt further clinical, biochemical and genetic studies will eventually curtail the activities of this elusive 'purple pimpernel' and its disguises.
I wish to conclude this short paper with the last four lines from Dean's book The Porphyrias' ? 'It has involved the study of the formation of a people, and has been an exciting voyage of discovery which still continues the everlasting whisper something hidden, go and find it'.